Thomas H. Stanisic

A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder

BACKGROUND In carcinoma of the bladder, both intravesical chemotherapy and immunotherapy can induce tumor regression and reduce the rate of recurrence, but the relative merits of these two therapies are unclear. We conducted a multi-institutional study to address this question. METHODS Patients with rapidly recurrent (stage Ta and T1) or in situ transitional-cell carcinoma of the bladder were randomly assigned to receive either doxorubicin administered intravesically or bacille Calmette-Guérin (BCG) administered both intravesically and percutaneously. The 262 eligible patients were followed for a median of 65 months. Complete responses to treatment of carcinoma in situ were confirmed by biopsy and cytologic analysis of the urine. RESULTS For patients with Ta and T1 tumors without carcinoma in situ, the estimated probability of being disease free at five years was 17 percent after doxorubicin, as compared with 37 percent after immunotherapy with BCG (P = 0.015). The median times to treatment failure (termination of treatment, due to persistence, recurrence, or progression of disease) were 10.4 and 22.5 months, respectively. For patients with carcinoma in situ the complete-response probability estimates (i.e., the estimated probability of documented disappearance of disease) were 34 percent for doxorubicin (23 of 67 patients) and 70 percent for BCG (45 of 64 patients) (P less than 0.001); the median times to treatment failure were 5.1 and 39 months, respectively. The probability of being disease-free at five years survival among the patients with carcinoma in situ was 18 percent after treatment with doxorubicin and 45 percent after BCG therapy. Patients treated with BCG had a higher incidence of toxic systemic effects and a larger number of local irritative symptoms than patients treated with doxorubicin, but few of these adverse reactions were severe. CONCLUSIONS As compared with intravesical doxorubicin, immunotherapy with BCG provides improved protection against the recurrence of superficial bladder cancer.

An in Vitro Clonal Assay for Bladder Cancer: Clinical Correlation with the Status of the Urothelium in 33 Patients

AbstractAn in vitro colony forming assay system is described in which urothelial cells obtained by bladder barbotage at cystoscopy are cultivated in nutrient enriched soft agar. In the 33 patients studied in vitro growth characteristics correlated with the clinical behavior of the urothelium in vivo. All 9 patients with bladder cancer confirmed by biopsy had in vitro growth. Only 3 of the 17 control patients with non-neoplastic urologic disease had clusters/colonies in vitro. In 2 of 7 patients with no conclusive evidence of transitional cell carcinoma at the time of cystoscopy in vitro cluster formation was predictive of subsequent malignant deterioration. Implications and potential applications of the assay system are discussed.

Intravesical bacillus Calmette-Guerin therapy and associated granulomatous renal masses.

We report a case of clinically symptomatic renal granulomas occurring during intravesical and intracutaneous bacillus Calmette-Guerin therapy for bladder cancer. The patient responded to antituberculous triple therapy. We emphasize the rarity of such extravesical infectious complications and discuss the possible routes of renal inoculation.

Prolactin Secreting Renal Cell Carcinoma

We report a case of hyperprolactinemia and long-standing gynecomastia associated with a hypernephroma. After radical nephrectomy serum prolactin returned to normal and remained so for 4 years without evidence of tumor recurrence. Potential explanations for the observed concurrent findings and the literature are discussed.

Above and Below Delayed Endoscopic Treatment of Traumatic Posterior Urethral Disruptions

Between 1982 and 1990, 10 men with posterior urethral obliterations associated with pelvic fracture were managed with delayed above and below endoscopic reconstruction. After a mean of 43 months (range 7 to 108) of followup, all 10 men void with a peak flow rate of 12 ml. per second or greater and/or have a urethral caliber of 20F or greater. Concomitant prostatic hypertrophy somewhat compromises micturition in 4 older men. Nine patients are totally continent and 1 has mild stress incontinence. Five men who were potent after injury remain so after reconstruction. Of the 10 patients 6 required subsequent visual urethrotomy and/or scar resections, generally as outpatient or short stay procedures. In most instances voiding stabilized within 1 year, and interventions after this interval were unusual and generally trivial. We compare our experience with the results of others using a similar delayed endoscopic approach and conclude that this is a satisfactory method of managing traumatic posterior urethral obliterations, resulting in satisfactory voiding, continence and potency preservation.

Epithelioid sarcoma of the penis.

A rare case of penile epithelioid sarcoma in a 26-year-old white man is presented. The patient had a firm, slow growing, painless mass associated with penile deviation on erection, which was initially misdiagnosed as Peyronies disease 5 years previously. With the onset of decreased urinary stream the lesion was biopsied, with a resultant diagnosis of epithelioid sarcoma. The patient underwent radical penectomy and perineal urethrostomy, and received 6,000 cGy. external beam radiotherapy postoperatively. Two years postoperatively the patient remained free of clinical disease. We review the pathophysiology, clinical characteristics and treatment of penile epithelioid sarcoma.

Cytogenetic Analysis of Urologic Malignancies: Study of Tumor Colony Forming Cells and Premature Chromosome Condensation

We have utilized a human tumor clonogenic assay to grow, and subsequently cytogenetically analyze, tumor colony forming cells from human urologic malignancies. Results following chromosome banding analysis are presented from 4 cases of transitional cell carcinoma and 1 case of renal cell carcinoma. Preliminary evidence suggests a possible association between the loss of chromosome 8 and progression or recurrence of transitional cell carcinoma. Additionally, we have utilized the technique of premature chromosome condensation to identify the interphase chromatin profile of urothelial cells obtained by cystoscopy from 8 patients with transitional cell carcinoma and compared these results to urothelial cells obtained from 7 control patients. This study demonstrates that cells obtained from urologic cancers contain a high proportion of cells in late G1, while normal urothelial cells are usually found in the early G1 phase of the cell cycle. Statistical correlation of premature chromosome condensation analysis suggests this method may be a useful adjunct to routine histopathology in discriminating between normal and cancerous urothelium.

Polytetrafluoroethylene Injection for Post-Prostatectomy Incontinence: Experience with 20 Patients During 3 Years

We treated 20 men who were incontinent after prostatectomy and who had failed sphincter exercises with periurethral polytetrafluoroethylene (Teflon or Polytef) injections. Injections were done with the patient under brief general or spinal anesthesia as an outpatient or during a 24-hour hospitalization. Incontinence was due to radical prostatectomy in 17 patients and simple prostatectomy for benign disease in 3. Most patients had more than 1 injection and mean followup was 17 months. Of the 20 men 7 (35%) reported long-term improvement and 4 (20%) recommend the procedure to others. Complications were limited to 1 spontaneously resolving 48-hour bout of urinary retention and 1 episode of perineal polytetrafluoroethylene migration that produced pain for 3 months. We found the procedure to be simple, generally well tolerated and capable of producing clinical improvement in a significant minority of patients in whom it was used.

The prognostic significance of S-phase analysis in stage Ta/T1 bladder cancer : A Southwest Oncology Group study

Objectives:An intergroup study (SWOG 8795) comparing two forms of adjunctive therapy (immuno and chemo), bacillus Calmette–Guerin (BCG) and mitomycin C (MMC), furnished preregistration index tumors for 244 patients with superficial, papillary stage Ta/T1 TCC. These were examined by flow cytometry to learn whether DNA ploidy or proliferation (low vs high S–phase fraction (SPF) helped to predict disease recurrence or progression.Methods: Cell cycle analysis using commercially available (Multicycle) programs was performed on 249 Ta/T1 bladder cancers. Tumor grade, available for 223 cases, was assigned by a single study pathologist. The SWOG statistical office reviewed follow–up information and other data and performed statistical analysis.Results: Disease recurrence occurred in half the cases studied. The most parsimonious model predictive of recurrence included only treatment arm and tumor grade, with the MMC arm and tumor grade greater than I indicating worse prognosis (p = 0.014). Neither ploidy nor SPF predicted recurrence–free survival or contributed prognostic information that was additive to tumor grade. Within 5 years of follow–up, disease progression or death from bladder cancer occurred for 29/223 (13%) of patients. The most parsimonious model for progression–free survival included only grade greater than I (p<0.001) and high SPF (p = 0.029) (relative risk: tumor grade, 4.3, high SPF, 1.9).Conclusions: Knowledge of tumor proliferation (low versus high SPF) contributes prognostic information about tumor progression that is additive to tumor grade.

Congenital Ureteral Valves: Report of 2 Patients, Including One With a Solitary Kidney and Associated Hypertension

We report 2 cases of congenital ureteral valves treated successfully by excision of the involved segment and ureteroureterostomy. Hypertension in 1 patient and recurrent urinary tract infection in the other prompted initial evaluation. In the hypertensive patient renin collections from the vena cava and the renal vein of the solitary kidney were normal. Nevertheless, relief of obstruction has resolved the hypertension for 3 years. We review the literature regarding ureteral valves and discuss the mechanism by which unilateral hydronephrosis probably produces hypertension.